Method and a system for administerinng muscle relaxant to a patient

ABSTRACT

The invention relates to a system for administering muscle relaxant to a patient. The system includes an infusion pump ( 102 ) adapted for delivering said muscle relaxant to a patient, and a controller ( 101 .) adapter for controlling the operation of said infusion pump on the basis of at least one received input value. Further the system includes measuring means ( 103 ) adapted for continuously measuring the effect of said muscle relaxant on the patient and adapted for supplying a value representing said measured effect as said input value to said controller. According to the invention, on basis of said at least one input value, said controller is adapted for selecting a control value from a set of predetermined control values as the value to be used for controlling said infusion pump. The invention also relates to a method of administering muscle relaxant to a patient and to a testing apparatus adapted to be used for testing the automatic operation of a system for administration of muscle relaxant to a patient.

TECHNICAL FIELD

[0001] The present invention relates to a system for administeringmuscle relaxant to a patient, said system including:

[0002] an infusion pump adapted for delivering said muscle relaxant to apatient,

[0003] a controller adapted for controlling the operation of saidinfusion pump on the basis of at least one received input value, and

[0004] measuring means adapted for continuously measuring the effect ofsaid muscle relaxant on the patient, and adapted for supplying a valuerepresenting said measured effect as said input value to saidcontroller.

[0005] The invention also relates to a method for administering musclerelaxant to a patient.

BACKGROUND ART

[0006] Skeletal muscle relaxants are administered to patients undergoingsurgical procedures in order to facilitate intubation and to providemuscle relaxation in the surgical field.

[0007] When muscle relaxants are used in the operating room, accordingto current practice, the muscle relaxant is injected into the patientmanually by an anesthesiologist. The effect of the muscle relaxant onthe patient, i.e. the so-called relaxation, is assessed either byclinical observations alone; subjectively quantified by use of aperipheral nerve stimulator (PNS); or it can be measured objectively bymeans of a neuromuscular transmission monitor. When the clinicalobservations/judgements or data from the monitor device indicate thatthe patient is sufficiently relaxed, the patient may be intubated tofacilitate automatic ventilatory support and the surgical procedure maybegin.

[0008] When the effect of the muscle relaxant begins to disappear ordecrease, meaning that the patient is becoming less relaxed, additionaldoses of muscle relaxant may be administered to the patient to ensuresufficient surgical relaxation and hereby enable the procedure tocontinue. The process of administering muscle relaxant to the patient isrepeated during the entire surgical intervention. When the interventionis finished, monitoring of the patient must continue during the recoveryphase. This is required, as the patient is not capable of breathing onhis/her own, until the muscle relaxation effect has disappeared. Duringthe surgical intervention and the recovery phase the patient isventilated to support proper supply of oxygen. When the physician judgesthat the patient is sufficiently recovered and the muscular function hasreturned, extubation will take place and the patient will breathe onhis/her own. It is noted that the physician may perform theabove-mentioned judgements by means of clinical observations, by use ofPNS, or by use of a neuromuscular transmission monitor.

[0009] As an alternative to the drug injection performed manually by ananesthesiologist, a semi-automatic infusion system can be used. Such asystem is disclosed in U.S. Pat. No. 5,256,156 to Kern et al. Thissystem, which is an infusion system for administration of neuromuscularagents and the like to a patient, includes a microcomputer-controlledinfusion pump with a data input pad. A clinician enters the desiredparalysis level and performs periodically an electro-stimulation test todetermine the actual paralysis level of the patient. This information isentered into the system by the physician, which system then calculatesand administers a new dosage.

[0010] On basis of an input value, the controller may be adapted forselecting a control value from asset of predetermined control values asthe value to be used for controlling said infusion pump.

[0011] U.S. Pat. No. 5,843,134 describes a medication-dosing devicehaving at least one sensor for detecting the physical state of a patientand for outputting a corresponding measured value, and an evaluating andcontrolling device adapted for determining a therapy control variablefrom the measured value. The device comprises an addressable dosage-datamemory including an association table for heart rate-medication dose.

[0012] “Automated Delivery of Muscle Relaxants using Fuzzy LogicControl”, Mason D. G. et al., IEEE Engineering in Medicine and BiologyMagazine, US, IEEE Inc. New York, vol. 13, no. 5, 1 November 1994, Pages678-686, describes a fuzzy logic controller adapted for controlling thedelivery of muscle relaxant to a patient. The fizzy logic controllerincludes a performance index look-up table. The inputs usuallyconsidered are the error from a desired reference value, i.e. thedifference between a measured level of the desired level of relaxationand the measured level of relaxation, and the change in this error. Theoutput is either considered to be the controller output or the change incontroller output. The level of relaxation of the patient is measured bysupplying a stimulation pulse to the patient and measuring the level ofthe resulting muscle reaction pulse.

[0013] Such systems can be useful, but some have the drawback ofrequiring constantly monitoring of the neuromuscular function andmanually entering the actual measured paralysis level of the patient,which is quite demanding for the personnel in the operation room. Othersystems have the drawback of relying on one resulting reaction pulseonly and require rather complex implementation means which can becumbersome to verify completely in all situations. Consequently thepatient may be given more muscle relaxant than actually required for thesurgical procedure. Alternatively if the patient is given too littlemuscle relaxant, the surgical conditions will also be sub-optimal. Noneof these situations are desirable, neither with respect to the comfortof the patient or from a surgical point of view. In addition thesesituations are undesirable from an economic point of view. The desire touse a complete automated neuromuscular blocking agent delivery systemwas also mentioned in the above U.S. Pat. No. 5,256,156 to Kern et al.However according to Kern et al., such a system is too cumbersome andexpensive to be clinically useful.

BRIEF DESCRIPTIONS OF THE INVENTION

[0014] It is an object of the invention to provide an improved systemfor administering muscle relaxant to a patient compared to the systemsknown from the prior art.

[0015] According to the invention, a system of the above-mentioned artis described, wherein said measuring means is adapted for stimulating amuscle of the patient by a number of succeeding electric or magneticpulses, for measuring the resulting muscle reaction pulses and for usingthe number of muscle reaction pulses as said input value.

[0016] The invention, which overcomes the prejudice of the prior artthat the construction of a system for administering muscle relaxant to apatient or an automated neuromuscular blocking agent delivery system istoo cumbersome and expensive to be clinically useful, is based on thefact that infusion can be controlled by use of a predetermined set ofcontrol values. Hereby a system according to the invention is madereliable as the operation of the infusion pump is restricted to theoperation associated with the predefined control values, i.e. a stableand reliable system is obtained. In addition, as the operation of theinfusion pump is restricted to the operation associated with thepredefined control values, the relatively simple system resultingtherefrom can easily be tested in order to prove a desirable operation.This is of major interest in relation to clinical use as the desirableoperation of the system can be validated and documented.

[0017] A system according to the invention has been found to have thefollowing advantages compared to prior art systems for administeringmuscle relaxant to a patient. In addition to the optimal surgicalconditions which can be achieved, a better control of the effect of thedrug is obtained compared to the use of manual dosing or the use ofknown semi-automated systems. In addition less workload is imposed onthe staff, and, as the dosing of the drug does not require constantattention of an anesthesiologist, an environment wherein more attentioncan be given to the well-being of the patient is achieved. Furthermore,an optimal drug load to the patient can be achieved, i.e. a minimalamount of drug to obtain the effect desired can be used, and as a resultthe fastest possible patient recovery after stop of drug infusion canalso be obtained.

[0018] Furthermore, as the system according to the invention is adaptedfor stimulating a muscle of the patient by a number of succeedingelectric or magnetic pulses, for measuring the resulting muscle reactionpulses and for using the number of muscle reaction pulses as said inputvalue, the patient's level of relaxation can be measured in a bothsimple, reliable and fail-safe manner. The invention is based on thefact that the resulting number of muscle reaction pulses has been foundto be a good indication of the patient's muscle relaxation. Furthermore,this solution enables a simple interface with the controller as theresulting number of reaction pulses may be used as input; i.e. theoperation of the infusion pump may be controlled using the resultingnumber of reaction pulses.

[0019] According to a preferred embodiment of the invention, the systemincludes a memory with an array of one or more dimensions holding saidset of predefined control values, where said controller is adapted forselecting a control value from said set of control values by indexingsaid array by said at least one input value and/or at least one valuederived therefrom. Hereby, as the contents of an array can be indexed ina simple way, the control values can easily and rapidly be retrieved andused for the control of the infusion pump.

[0020] Preferably, said array is adapted for including one or moremathematical functions as a representation of a number of said controlvalues. Hereby, as a number of control values may be stored as a reducednumber of mathematical functions compared to the number of controlvalues represented hereby, the memory requirement is kept at a minimum.Further, when continuously mathematical functions are used, a controlvalue between two discrete indexing values may easily be computedwithout interpolating using two or more discrete control values.

[0021] According to another preferred embodiment of the invention, saidcontroller is adapted to select the control value or a representationthereof on the basis of at least one index value derived from two ormore previously received input values. Preferably said at least oneindex value is derived as the mean value of two or more previouslyreceived input values. Hereby a high resolution of the received inputvalue is obtained in a simple manner even when only a single input valueis received from the measuring means. For example, even when a simpleinput value of integer type is received from the measuring means, ahigher resolution is obtained by use of the value derived from a numberof previously received values.

[0022] According to a preferred embodiment of the invention saidmeasuring means is adapted for comparing two or more of said measuredmuscle reaction pulses with two or more corresponding reference musclereaction pulses or a representation thereof, and determining thedifference there between as an effect of direct muscle stimulation.Hereby, a possible direct stimulation of the muscle, e.g. due to anincorrect locations of the stimulation means in relation to the patient,can be detected by the system.

[0023] Preferably, said system is adapted for subtracting said effect ofdirect muscle stimulation from the measured effect of said musclerelaxant delivered to the patient. Hereby, it is ensured that a correctdetermination of the effect of the muscle relaxant on the patient isperformed, and as a consequence, that an optimal amount of musclerelaxant is delivered to the patient.

[0024] According to yet another preferred embodiment, said infusion pumpis adapted for incepting a container including muscle relaxant, and fordelivering muscle relaxant from said container to a patient, and byfurther including identification means adapted for identifying, thecontainer incepted in the infusion pump. Hereby it can easily be ensuredthat the desired container, i.e. a container including the desired typeof muscle relaxant, is incepted in the infusion pump and an undesireduse can be avoided.

[0025] When said controller furthermore includes a plurality of sets ofcontrol values, and said controller is adapted for selecting a set ofcontrol values to be used on the basis of the identification of thecontainer incepted in the infusion pump, the operation of the system canbe optimized in accordance with the given container and hereby with thecontents of the given container.

[0026] Preferably, said controller includes a plurality of sets ofcontrol values, and said controller is adapted for selecting a set ofcontrol values to be used on the basis of a received value representingthe type of intervention performed or to be performed or is dependentupon certain specific patient characteristics. This solution is ofinterest as a further security check can be performed based on thereceived information. The security may be further improved, when drugidentification information and/or patient specific information is alsoreceived in the system or accessible by the system.

[0027] As described above the invention also relates to a method ofadministering muscle relaxant to a patient, said method including:

[0028] delivering said muscle relaxant to a patient, where saiddelivering is controlled on the basis of at least one received inputvalue, and

[0029] continuously measuring the effect of said muscle relaxant on thepatient, and supplying a value representing said measured effect as saidinput value for said controlling, wherein:

[0030] said controlling is performed using a set of predeterminedcontrol values, and further including

[0031] selection of a control value from said set of control values asthe value to be used for controlling said infusion pump, where saidselection is based on said input value and/or a value derived therefrom.

[0032] The advantages of the method according to the method describedabove and according to the methods of the preferred embodiments ofclaims 12 and 13 will not be described as they are already described inconnection with the corresponding system claims.

[0033] Furthermore, the invention relates to a testing apparatus adaptedto be used for testing the operation of a system for administeringmuscle relaxant to a patient. This is of major interest as the test ofsuch systems has to be performed and documented prior to the actual use.Therefore, a system which can ease this cumbersome task is of majorinterest.

[0034] The testing apparatus according to the invention is characterisedby including:

[0035] an input emulator adapted for receiving muscle relaxant from saidsystem;

[0036] a testing signal receiver adapted for receiving a testing signalfrom said system;

[0037] a test controller adapted for continuously determining a valuerepresenting the present level of relaxation of a patient simulated bythe apparatus, said value being determined on basis of the amount ofrelaxant infused and the time elapsed since infusion; and

[0038] a response emulator adapted for generating an output signal inresponse to said received testing signal, said output signal reflectingthe present state of relaxation.

[0039] A testing apparatus according to the invention enables anevaluation and validation of the widest possible range of patientinteractions in a pre-clinical in-vitro setting. Further advantages aswell as preferred embodiment of the system according to the inventionwill be described in the detailed description below.

BRIEF DESCRIPTION OF THE DRAWING

[0040] Other features and advantages of the present invention willbecome apparent from the following description of the preferredembodiments, taken in conjunction with the accompanying figures wherein:

[0041]FIG. 1A is a system according to the invention,

[0042]FIG. 1B illustrates a closed loop system according to theinvention,

[0043]FIG. 2 illustrates the infusion pump part of a system according tothe invention in more details,

[0044]FIG. 3A is an example of a one-dimensional array holding a set ofpredefined control values,

[0045]FIG. 3B is an example of two-dimensional array holding a set ofpredefined control values,

[0046]FIG. 3C illustrates a three-dimensional array holding a set ofpredefined control values,

[0047]FIG. 4 illustrates a preferred control of the delivery of musclerelaxant to a patient,

[0048]FIG. 5 illustrates a preferred control of the delivery of musclerelaxant and an initialisation thereof,

[0049]FIG. 6 is a test system according to the invention, and

[0050]FIG. 7 is an example of a determination and correction of ameasured effect of direct muscle stimulation.

BEST MODE FOR CARRYING OUT THE INVENTION

[0051]FIG. 1A is a system according to the invention, i.e. a system foradministering muscle relaxant to a patient. The system 100 includes aninfusion pump 102, a controller 101, and measuring means 103. Theinfusion pump 102 is adapted for delivering the muscle relaxant to apatient, and the measuring means 103 is adapted for continuouslymeasuring the effect of the muscle relaxant on the patient. Themeasuring means 103 is connected to the controller 101, e.g. via a datachannel connection, and is adapted for supplying a value representingthe measured effect of the muscle relaxant on the patient to thecontroller 101. For example, the data channel connection can beimplemented as an RS-232 connection. The controller 101 is adapted forcontrolling the operation of said infusion pump 102 on the basis of thevalue received from the measuring means 103.

[0052] The controller 101 includes a first memory 105A holding a set ofpredetermined control values, and the controller is adapted forselecting a control value from the set of control values as the value tobe used for controlling said infusion pump 102. The selection of thecontrol values from the set of control values is described in thefollowing. In another preferred embodiment the system includes a secondmemory 105B in which the predetermined control values or at least a partthereof is located. As illustrated in the figure, the controller isconnected to the second memory or is adapted to being connected theretowhen needed. For example, the second memory 105B may be a hard discdrive, a RAM, a ROM, a CD-ROM, or another type of memory being able tohold predetermined control values.

[0053] In a preferred embodiment, the controller and the second memory105B is connected via a network connection. This enables a number ofsystems to share the same second memory, and hereby the predeterminedcontrol values can be stored and updated centrally. Further, this isadvantageous as the size of a local memory, e.g. located in thecontroller or in direct connection with the controller, can be reducedto a size enabling it to hold a single set of control values, forexample. The external memory on the other hand can hold a large numberof sets of control values, and the system can be adapted to retrieve theset of control values to be used either on the ran or prior to theadministration of the muscle relaxant to the patient. Due to safety thelatter of these two solutions is often advantageous.

[0054] As illustrated in FIG. 1B, the system according to the inventionis a closed loop system wherein the controller 101 is connected to theinfusion pump 102. When the infusion pump 102 is connected to a patientmuscle relaxant can be delivered to the patient via the infusion pump102 under the control of the controller 101. The measuring means 103 iscontinuously measuring the effect of said muscle relaxant on thepatient. The measuring means 103 is also connected to the controller 101to which it supplies the obtained measurements. The controller 101 usesthe received measurements to control the amount of muscle relaxant to bedelivered to the patient.

[0055] The controller 101, which is also called a controller unit in thefollowing, is adapted for controlling the operation of said infusionpump 102 on the basis of a received input value. In the example shown,the controller unit 101 receives information about the patient's stateof relaxation from the measuring means 103 and inputs the receivedinformation to a control array containing values for a predefineddesired level or target level. Based upon the actual level of relaxationand the specific selected control values, the controller 101 determinesthe amount of relaxant to be used in the further dosing in order toreach the target state. The controller unit 101 then commands the pump102 to maintain, increase or decrease the amount of relaxant infused tothe patient. The determination is performed by use of a controlalgorithm which is described in the following.

[0056] The measuring means 103, which is also denoted the neuromusculartransmission monitor 103 or simply the monitor 103 in the following,measures the patient's level of relaxation, and supplies the measuredeffect as one or more input values to the controller 101. In a preferredembodiment of the invention, the measurement is performed by applying asmall electrical stimulation pulse to the patient and measuring themuscle reaction as the result of the applied stimulation. It is notedthat the stimulation may also be applied to the patient in other ways,e.g. by a magnetic excitation of the nerve controlling the muscle to beelicited.

[0057] The measuring means 103 includes means for applying a smallelectrical impulse (stimulation) to the patient and measuring means,such as an acceleration transducer, which is adapted for measuring themuscle reaction as the result of electrical stimulation. The adductorpollicis muscle is normally used for routine neuromuscular transmissionmonitoring, and in this case the muscle reaction generates a movement ofthe thumb and an acceleration transducer measures the acceleration ofthe thumb. It is noted, that other muscles can be used as well in orderto measure the relaxation of the patient; e.g. the orbicularis occuli,the corrugator supercilii or the flexor hallucis brevis etcetera musclesmay be used.

[0058] The size of the muscle reaction is proportional to the patient'sstate of relaxation.

[0059] Muscle reaction can be quantified either by measuring the force(MMG) from the muscle reaction (isometric), the generated acceleration(AMG), the evoked muscle potential (EMG) or measuring the evokedacoustic muscle signal from the contraction (Phono myography). Themonitor. 103 transmits the measured relaxation data to the controller101 of the system.

[0060] The neuromuscular transmission monitor 103 may be derived from analready commercial available device (e.g. TOF-Watch® SX from NVOrganon), with adaptations to accommodate for the actual application.This microprocessor-controlled monitor is designed with the necessaryredundant protection against stimulation (current) that is too high,open circuit stimulation, watchdog circuitry for microprocessormonitoring etc. The monitor 103 transmits the measured relaxation datato the controller unit 101 of the system.

[0061] The infusion pump 102 may be a syringe pump, i.e. a pumpincluding a mechanism for driving or pushing a normal syringe, or avolumetric pump. A volumetric pump can be constructed either as a rollermechanism—also called a peristaltic pump—or a set mechanical fingersactuating a flexible tubing containing the drug or a membrane pump.

[0062] The pump 102 to be used may be derived from a standardcommercially available pump, with adaptations to identify the drug beinginfused by the system. Like the other elements in the system, the pump102 may be microprocessor controlled and designed with the requiredredundancy towards occlusion, drug container in place, near emptydetection, drug container identity etc. The controller unit 101 of thesystem will command/control the infusion of drug via the pump 102.

[0063] The controller unit 101 receives information about the patient'sstate of relaxation from the monitor 103 and inputs the received valuesto a control array containing values for the desired level ofrelaxation. Based upon the actual level of relaxation and the desiredlevel from the specific selected control array, i.e. the target level,the controller 101 determines—by use of the control algorithm—furtherdosing to reach the target state of relaxation. The controller unit 101then commands the pump 102 to maintain, increase or decrease the amountof relaxant infused to the patient.

[0064] The controller unit of the system may also contain various safetymechanisms to ensure that possible errors will not result in asubstantial over/under dosing of the patient. As for the other elementsin the system, redundancy mechanisms can also be incorporated in thecontroller.

[0065] Finally, the controller unit 101 also contains the controlinterface towards the user and performs registration of all events anddata being registered during use. This is indicated in FIG. 1B whereinthe system also includes a user interface which may be used by a user109, such as a physician being in contact with the patient 110. Asillustrated, the user interface may include input means, such as akeyboard 107, by which the user 109 may be able to input relevantinformation and output means, such as a display, by which the user 109can be presented by system information, e.g. information of thepatient's relaxation. For example, for security reasons, the user 109may be able to adjust or even halt the regulation.

[0066] The measuring means is adapted for stimulating a muscle by asingle or a number of succeeding electric or magnetic pulses, formeasuring the resulting muscle reaction pulses, and for using the valueof the reaction pulses and/or the number of muscle reaction pulses asthe input value to the controller. In one embodiment the stimulationincludes a number of pulses which are repeated at a constant rate, butin another embodiment the stimulation includes a number of pulses whichare repeated at a varying rate.

[0067] As described above, the controller or controller unit 101 isadapted for controlling the operation of said infusion pump 102 on thebasis of at least one received input value. The input value or the inputvalues are received from the measuring means 103 and are used in orderto retrieve the control values to be used when controlling the operationof the system. The control values are retrieved from the first or secondmemory 105A, 105B.

[0068] According to another preferred embodiment of the invention, thecontroller 101 is adapted to select the control value on the basis of anindex value derived from the last and/or two or more previously receivedinput values, and preferably from a set of index values derived from acombination of the last and two or more previously received inputvalues. Preferably said index value is derived from the mean value oftwo or more previously received input values. Hereby a high resolutionof the received input value is obtained in a simple manner even whenonly a single input value is received from the measuring means. Forexample, even when a simple input value of integer type is received fromthe measuring means, a higher resolution is obtained by use of the lastvalue and a combination of values derived from a number of previouslyreceived values. It is noted that the index value can be derived frompreviously received input values in other ways as well, e.g. asexponential average, gradient (slope), higher order derivatives.

[0069]FIG. 2 illustrates the infusion pump part of a system according tothe invention in more details. As described previously, an infusion pump102 being adapted to transfer muscle relaxant to a patient is connectedto and controlled by a controller 101, such as a micro-processor. Asillustrated in the figure, a drug container 201 containing a drug to besupplied to a patient may be attached to the infusion pump 102 which hasbeen developed for this purpose. Hereby, the drug to be used can easilyand quickly be replaced when needed. Even though only a single drugcontainer is shown in the figure, a larger number of containers may beconnected to a system according the invention if desired.

[0070] The infusion pump also includes supplying means connecting theinfusion pump to the patient, e.g. via an infusion set supplyinginfusion fluids and the like to a vein of the patient. As illustrated inthe figure, an identification of the drug container 201 incepted in theinfusion pump 102 is performed by use of identification means 202 in thesystem. The identification means 202 is adapted for identifying the drugcontainer incepted in the infusion pump 102 and hereby identifying thecontents of the drug container 202. In a preferred embodiment, theidentification is performed using a drug ID tag 204 attached to the drugcontainer 201. The drug ID 204 tag contains information relating to themuscle relaxant in the drug container 201. For example, the drug ID tag204 may include information, such as the type of drug, the date ofproduction, the time of production, the date for last use, the time forlast use, and/or concentration information.

[0071] The identification may be performed in a number of ways in whichthe drug container 201 holds identification information which can beread or received by identification means 202 located in the system. TheID tag 204 may include a bar code holding the identification informationand consequently the system may include a bar code reader as anidentification means 202. The identification may also be performed byuse of other types of ID tags 204 and other types of identificationmeans 202. The information means 202 may also be adapted to read orreceived identification information from other types of ID tags 204,such as reading of a magnetic stripe—contact reading, electronic readingof memory—electric contact reading, magnetic label—space readable (nocontact required to label), RFID (Radio Frequency Identification)—chipwith coil (magnetic actuation) or antenna (electrostatic actuation),and/or mechanic coding and mechanic reading. As will become clear fromthe following description, the possibility of identifying the drugcontainer 201 is of major interest according to the invention. Forexample, based on a performed drug identification, an array of controlvalues may be selected from a plurality of arrays of control values. Theselection of an array of control values may also be based on a drugidentification in combination with patient related information.

[0072]FIG. 3A is an example of an array or table of one dimensionholding a set of predefined control values. The system has access to thecontrol values in the array and uses the control values in order toperform the drug delivery control. Therefore, the array may be locatedin the memory of the controller, and/or in another accessible memory.The control values of the array may be retrieved by use of an indexvalue; e.g. using an input value reflecting the patient's state orrelaxation or a value derived therefrom as an index value.

[0073]FIG. 3B is an example of two-dimensional array holding a set ofpredefined control values. In order to perform a look-up in the array ortable, two index values may be used. A first index value may for examplebe used as a first entry, e.g. pointing out a row in the table, and asecond index value may for example be used as a second entry pointingout a column in the table. As described in more details in thefollowing, different values may be used as index values, e.g. a valuereflecting the patient's state of relaxation or a value derivedtherefrom.

[0074]FIG. 3C illustrates a three-dimensional array holding a set ofpredefined control values. According to the figure, the array may alsobe three-dimensional allowing three index values to be used whenselecting a control value to be used. Likewise, an array of higherdimension may be used as well. The use of more dimensions enables theuse of different parameters when selecting control values which may beadvantageous, but in the preferred embodiment a dimension of two orthree has been found optimal in most cases due to simplicity.

[0075] The relationship between one or more input values reflecting thestate of relaxation of the patient in a given period of time or one ormore values derived therefrom, and the control value to be supplied tothe infusion pump in order to achieve or maintain a desired level ofrelaxation is very complex. The relationship can be described by acomplex mathematical formula specifying a surface of control values inan n-dimensional space defined by the input values used and the valuesderived therefrom. As the mathematical relation is very complex, anarray is used in order to define the control values.

[0076] Due to the complexity of the regulation system, the determinationof the control values is very computation power demanding. Therefore,the array to be used when administrating muscle relaxant to a patient ispredetermined, i.e. the computation of the control values is performedprior to the use of the system. For example, the manufacturer of thesystem may perform the computation as the computation time in this phaseis less critical than the computation time during use of the system. Byperforming the computation or at least a major part thereof prior to theuse of the system, the regulation may be performed sufficiently rapid toobtain a good regulation. Further, by predetermining the control values,a stable and secure system can be achieved as the behaviour in ailpossible situations can be tested.

[0077] In order to determine the control values to be used in an array,a large number of data sets describing a pharmacokinetic,pharmacodynamic patient model, i.e. a PK/PD-model, for a number ofdifferent persons are used. The PK/PD-model, which is known from theprior art, describes a given body's influences on a given drug suppliedthereto (the pharmacokinetic part of the model), and how a given bodyreacts to a given drug concentration (the pharmacodynamic part of themodel). For example, the pharmacokinetic part describes how quickly thesupplied amount of drug is distributed (circulated) and eliminated inthe body, whereas the pharmacodynamic part describes the effect(relaxation over time) related to a given drug concentration at the siteof action for a given patient.

[0078] Based on a given target relaxation value the control values arecalculated and selected in accordance to a number of requirement. Therequirement must be selected in accordance with a number of decisions tobe taken. The decisions may for example be related to the followingtopics: (1) the regulation time (fast/slow regulation), (2) the amountof overshoot acceptable prior to achieving the desired level ofrelaxation, (3) good performance on abnormal patients too, (4) immunitytowards artifacts (noise) in the measurements. Depending on the choicesmade, the computation results in an array to be used when controllingthe system. Further, the control values are selected in such a way thata stable control system is obtained, e.g. when a given level ofrelaxation is reached, the control values to be used shall ensure thatno deeper or lower levels of relaxation can be achieved.

[0079] It is noted that an array of control values includes a number ofdiscrete control values in the preferred embodiment, but otherrepresentations may be used as well, if desired. For example, an arrayincluding predefined mathematical functions being sufficient simple topractical use may be used as well.

[0080]FIG. 4 illustrates a method or control algorithm according to theinvention, i.e. a method of administering muscle relaxant to a patient.The amount of muscle relaxant delivered to the patient is controlledcontinuously and the muscle relaxant is delivered to the patient by useof an infusion pump according to normal praxis. But it is noted that thedrug may be delivered in other ways as well, e.g. by inhalation,transdermal delivery or alike, if the drug used enables such a solution.The measured effect of the supplied muscle relaxant on the patient ismeasured continuously, and a value representing the measured effect issupplied as an input value, which is used for controlling thedelivering. The controlling is performed using a set of predeterminedcontrol values, and a control value from the set of control values isselected as the value(s) to be used for controlling said infusion pump.As will become clear from the following, the selection is based on saidinput value and/or a value derived therefrom.

[0081] After starting the control of the administering of musclerelaxant to a patient in step 401, the state of relaxation is measuredin step 403. The measurement in step 403 may be performed in a number ofways according to the prior art, e.g. by a small electrical stimulationto the patient and-measuring the muscle reaction as the result ofelectrical stimulation. Prior to the measurement performed in step 403,an initial predefined infusion of muscle relaxant to the patient may beperformed in step 402, but it is noted that due to safety no initialinfusion is normally performed prior to the determination of therelaxation in step 403. In step 404 the infusion rate to be used isdetermined, and in step 405 the infusion is started. It is noted that acontinuous infusion enables a slowly changing drug delivery.

[0082] In another preferred embodiment a discontinuous drug delivery isperformed in step 405, i.e. a given amount is infused in a given periodof time, only. This latter solution enables a more quickly change inrelaxation which is advantageous in some situations. In step 406 it isdetermined whether the regulation should be stopped, e.g. as a result ofan input from a user demanding the regulation to be terminated. Whenthis is not the case, the control is continued in step 403 in which thestate of relaxation is determined as described above. It is noted that adelay is advantageously inserted between step 406 and step 403 herebyenabling the drug inserted to have an effect on the patient beforedetermining the effect thereof. In the case in which the regulationprocess is halted the regulation is stopped in step 407. Step 406illustrates that the regulation may be halted as a result of a pollingperformed. Advantageously, a halt command, e.g. as a result of a userpressing a stop button, may be initiated as an interrupt command.

[0083] As illustrated in the figure, the determination of the infusionrate in step 404 may be performed in the following way. The state ofrelaxation information or result obtained in step 403 is received as aninput value in step 408 which is used as a first index value in step.410. The state of relaxation information or result obtained in step 403is also received as an input value in step 409. In step 409 an indexvalue is derived from the last and a number of previously received inputvalues, and the derived index value is used as a second index value instep 410. In the preferred embodiment the index is derived as the meanvalue of two or more previously received input values, e.g. as anaverage over a given interval of time such as two minutes. It is notedthat the index value can be derived from previously received inputvalues in other ways as well, e.g. as exponential average, gradient(slope), higher order derivatives based on a number of previouslyreceived input values.

[0084] In step 410 one or more control values are retrieved from alook-up table or array of control values using the index values fromstep 408 and 409. Based on the retrieved control value(s), the infusionrate is determined in step 415, and the infusion regulated in step 405.Likewise, the amount of muscle relaxant may be determined in step 415and the determined amount may be infused in step 405, if the musclerelaxant is delivered discontinuously.

[0085] As can be seen from the figure, the control table look-up isperformed from a table or array using two index values; i.e. atwo-dimensional table as illustrated in FIG. 3B may be used. Such animplementation is advantageous as the control algorithm and becomes bothvery simple and highly predictive under all conditions. This isessential in relation to the verification and validation of the systemscontrol performance.

[0086] Preferably, a number of index values is used when indexing thelook-up table and the index values used are a number of received inputvalues, e.g. the last and/or one or more previously received inputvalues, and/or a number of index values derived from a number ofreceived input values. The use of both one or more input values(preferably including the input value received lastly), and one or morevalues derived from one or more input values is advantageous and itenables the use of information reflecting the detected relaxation at agiven point in time as well as information reflecting the development inrelaxation over time. Hereby a smooth regulation towards a desired stateof relaxation may be achieved in a simple manner. For example, the useof a two-dimensional array holding control values which is indexed by afirst index value reflecting the present state of relaxation and asecond index value determined as a mean value of a number of previousreceived values reflecting the state of relaxation over a given periodof time has been found advantageous due to the simplicity, i.e. the lowcomputation requirements during control.

[0087] The use of stimulation pulses when determining the patient'sstate of relaxation has been found very useful. In a preferredembodiment the patient is given a predefined number of stimulationpulses, e.g. a number of pulses between 1 and 10 or more, and the numberof reaction pulses from the patient as a result of the stimulation ismeasured. Therefore, as the number of measured reaction pulses has beenfound to reflect the state of relaxation of the patient, the measurednumber is used as the input value in this embodiment, i.e. the selectionof control values is based on the measured numbers of reaction pulses.This solution has been found advantageous both due to the simplicity andthe robustness. When indexing an array of control values by use of aninteger, i.e. the measured number of reaction pulses, the resolution ofthe regulation is limited, i.e. a maximum number of control values givenby the number of stimulation pulses can be selected by use of a singleinput value. Therefore, according to the invention, the use of two ormore input values has been found advantageous when indexing the array ofcontrol values. In fact, the use of one or more index values derivedfrom one ore more input values has been found very useful as thissolution enables a higher resolution. For example, the use of a meanvalue has been found very useful. As mentioned above, one or more inputvalues may advantageously be used in combination with one or more valuesderived from a number of input values.

[0088] According to a preferred embodiment of the invention the controlmethod also includes a processing and checking step (step 420). Step 420includes the steps 411-414. In step 411 an interpolation, such as anlinear interpolation, is performed using a number of control valuesreceived from the array. This is advantageous when a value to be used asan index value does not correspond to a possible input value. Forexample, if an array of control values is to be indexed by use of aninteger value, e.g. in the interval between 1 and 5, and if the value tobe used as an index value is a real value, e.g. the value 2.4, thecontrol value to be used may be found by use of interpolation. Forexample, the control value corresponding to the control value associatedwith the control values 2 and 3 is retrieved from the array, and thecontrol value corresponding to an index value 2.4 is found byinterpolation, e.g. linear interpolation. In other words, the controlvalues in the array can be regarded as points on a surface of controlvalues in an n-dimensional space, where n is the dimension of the arrayof control values used. Therefore, the interpolation in step 411, can beregarded as an estimate of a point on the surface which is based on anumber of known control points on the surface.

[0089] In the shown embodiment, step 411 is followed by step 412 whereina volume/time limit check is performed. In step 412 it is ensured thatthe given patient is not given too much muscle relaxant; e.g. it isensured that the amount of drug delivered to the patient during apredefined period of time do not exceed a given limit. Preferably, thelimit is determined by the system by use of patient information such asbody weight or other relevant information. For example, the limit isdetermined during initialisation of the system.

[0090] In step 413, a weight and concentration adaptation is performedon the control values to be used, i.e. the control value is adjustedaccording to the given situation, e.g. by use of patient and druginformation. In the preferred embodiment, the control value andtherefore the amount of drug supplied to the patient is adjustedaccording to the weight of the patient. Hereby, a heavy patient may begiven a larger amount of drug, i.e. a larger control value is used,compared to a less heavy patient. Advantageously, the control value isadjusted according to the concentration of the drug used. Hereby, thesame array of control values may be used in the two situations wherein agiven drug used has a first and a second concentration, respectively.Therefore, the control values retrieved in the two situations can beadjusted differently when the first concentration is different from thesecond. This is of major interest as the memory requirement is reducedas a consequence of the possibility of using the same arrays of controlvalues in different situations. The adaptation may also be based onother patient and/or drug related information if desired. The adjustmentof the control values may be performed in different ways, e.g. as alinear adjustment. It is noted that other adjustment methods may be usedin order to obtain the desired relaxation of the given patient whenusing the given drug. Advantageously, the adaptation in step 413 isperformed using drug identification information received from the drugcontainer, i.e. drug information such as type, concentration may bereceived from the drug container.

[0091] Finally, in step 414, a boundary check is performed. This checkis performed as an additional security check ensuring that the amount ofdrug supplied to a patient does not exceed a specified limit at any timeand in any situation. As mentioned in relation to the previous step, thedrug identification information may also be used in this step. Hereby,the limit to be used can be based on information from the drugcontainer. According to the preferred embodiment, in order to increasethe safety of the system, the value used, e.g. a value derived orretrieved from the drug container information, is compared with valuespre-stored in the system. If an unacceptable difference between thevalue to be used and the pre-stored value an alarm is activated, and ifthe delivery of the drug is in progress the delivery may be interrupted.

[0092] As mentioned in more details below, the drug identificationinformation is advantageously retrieved in an initialisation phase, i.e.when initialising the system prior to the initiation of the actual drugdelivery. Hereby, it is ensured that the procedure is not started if thedrug identification retrieved is found to be abnormal.

[0093] It is noted that the processing and checking steps performed instep 411-415 are advantageous as the control of the delivery of musclerelaxant to a patient performed hereby has been found both very reliableand still performed in a simple manner which again ensures reliability.But it shall be stressed that the control may be performed in other waysas well. For example, the volume/time limit test of step 412 may beperformed in step 414 as well. Further, more or less steps could beincluded in the control algorithm if desired.

[0094]FIG. 5 is an example of the control of a system adapted fordelivering muscle relaxant according to the invention, and theinitialisation of such a system. In step 501, the control of system isstarted, e.g. when starting up the system or prior to the use of thesystem on a new patient. In step 502, the system is initialised. Theinitialisation may include inputting patient specific information intothe system, e.g. via an input pad such as the keyboard 107, retrievingdrug identification information, e.g. by use of identification mean 202as described in connection with FIG. 2. Further, an array of controlvalues may be selected from a plurality of control arrays of controlvalues accessible by the system; i.e. the arrays may for example belocated in the memory 105A and/or the memory 105B. During theinitialisation in step 502, the selection of the array is performed byuse of the drug identification information, the user specificinformation, and/or the type of intervention to be performed. Theselection based may be performed automatically by the system, e.g. by atable-lookup when the selection is based on drug identificationinformation and/or some patient information, whereas the selection maybe performed manually by a user, e.g. via an input means, such as akeyboard, when the selection is based on the type of intervention to beperformed or patient information indicating an abnormal and/or acritical situation. In such a situation, an alarm may be activated. Forexample, an alarm may be activated when the drug to be used is notusable for the actual patient. Such a test may for example be performedduring initialisation of the system by performing a table look-up in atable defining non-acceptable combinations of drug and patient types andthe like. Further, in a preferred embodiment the limit value used inconnection with the boundary check in step 414 is set using the drugidentification information and/or the user specific information. It isnoted, as an alternative to the weight and concentration adaptationperformed in step 413, such an adaptation or a part thereof may also beperformed during the initialisation step 502.

[0095] Preferably, said measuring means is adapted for detecting apossible direct stimulation of the muscle which may occur, eg. due to anon-optimal location of stimulation means on the patient. Direct musclestimulation, which circumvents the normal neuromuscular transmissionpathway, is a situation that often shows up during use in the clinic.When direct stimulation is present this will lead to an underestimationof the muscle relaxation level, which again may lead to an overdosing ofthe patient. A system that can detect and warn the user about a possibledirect stimulation will improve the safety when using muscle relaxationdrugs. By using a number of succeeding electric or magnetic stimulationpulses, instead of the commonly used single stimulation pulse, andhereafter analysing the ratios, fade or alike of these pulses it is madepossible to detect and warn about a possible direct stimulation. Suchdetection can be performed by comparing the measured responses with thecorresponding responses that are valid or normal when no directstimulation is present at the given relaxation level. Hereby a possibledirect stimulation can be detected and signalled to the user of thesystem.

[0096] Preferably, as illustrated in FIG. 7, the above-mentionedmeasurement of the state of relaxation (step 403 in FIG. 4) may beperformed in a way in which the effect of direct muscle stimulation istaken into account. As described in the following, the effect of directstimulation may be determined when a muscle is stimulated by a number ofsucceeding electric pulses. Further, as shown in FIG. 7, the detectedinformation may be used to correct the measured relaxation of the muscleand hereby obtain a more reliable result reflecting the actualrelaxation. The system according to the invention is adapted forperforming the described methods.

[0097] In the example shown in FIG. 7, the method includes a first step403 a in which a muscle of the patient is stimulated by a number ofsucceeding electric or magnetic pulses. The resulting muscle reactionpulses are measured as described above. In step 403 b two or moremeasured muscle reaction pulses, a representation thereof or informationderived therefrom are compared with the corresponding information ofreference muscle reaction pulse, i.e. information reflecting musclereaction pulses when no direct stimulation occurs. The referenceinformation, i.e. information reflecting one or more so-called normalresponses when supplying a patient with the given stimulation, isretrieved in step 403 c.

[0098] In the shown embodiment the normal responses are determined priorto use of the system and information reflecting the normal responses isstored in the memory of the system. In order to determine the normalresponses without any direct stimulation present, a large number of datasets describing a pharmacokinetic, pharmacodynamic patient model, i.e. aPK/PD-model, for a number of different persons are used. ThePK/PD-model, which is known from the prior art, describes a given body'sinfluences on a given drug supplied thereto (the pharmacokinetic part ofthe model), and how a given body reacts to a given drug concentration(the pharmacodynamic part of the model).

[0099] As mentioned above, the measured responses and the normalresponses are compared in step 403 b and the difference there between isused in step 403 d wherein it is determined whether the measuredresponses correspond with the responses of a normal situation. If thisis the case no further steps have to be performed and the measuredresponse may therefore be used as an input for said controller, i.e. themeasured response may be used as a measurement of the muscle relaxation.On the other hand, if an abnormal situation occurs, i.e. the measuredresponses and the normal responses are found to reflect different levelsof relaxation, the user of the system is given a waring (step 403 e). Instep 403 f the effect of direct stimulation is determined. Thedetermination may for example be calculated by comparing the measuredratios, fade or alike to a number of succeeding stimulation pulses andwith the responses that are present for the same muscle relaxation levelwithout direct stimulation. As described in connection with step 403 g,the measured responses can then be corrected to a value more trulyrepresenting the correct muscle relaxation level without directstimulation influence and the corrected value can then be used as aninput for said controller.

[0100] In step 403 g the responses are corrected by subtracting saideffect of direct muscle stimulation from the measured effect of saidmuscle relaxant delivered to the patient. The system according to theinvention may be adapted to perform the correction in the following way.The measured number of resulting pulses is corrected to a value morecorrectly representing the level of muscle relaxation without directstimulation being present.

[0101]FIG. 6 illustrates a test system 600 for testing a system forautomatic administration of muscle relaxant to a patient according tothe invention. The test system 600, which is also called a patientsimulator or an artificial patient (AP) in the following, emulatesphysical patient responses to the infusion of a muscle relaxant and theuse of a neuromuscular transmission monitor.

[0102] This artificial patient includes interfaces corresponding tothose of a real patient. As will be described in the following, the mainunits of the artificial patient are a balance or a flow measuring devicemeasuring the infused amount of muscle relaxant over time, the variableskin resistance measuring the electrical stimulation by the system andemulating the skin (electrode) contact, an incubator emulating the skintemperature of the patient to interface with the skin temperature sensorof the system and an acceleration generator, a force generator, a soundgenerator or an electromyography generator emulating the muscle signalresulting from the muscle contraction or reaction of the patient. Themuscle signal will be calculated from the measurements by software thatconsists of a pharmacokinetic, pharmacodynamic patient model developedfor the purpose.

[0103] The patient simulator 600 includes a test controller 602, aninput emulator 603, such as a weighing instrument or a flow measuringdevice, a skin temperature emulator 604, a response emulator 605, suchas an acceleration generator, a force generator, a sound generator or anelectromyography generator, and a variable skin resistance emulator 606.The patient simulator 600 is adapted to interact with a system foradministering muscle relaxant to a patient according to the invention.Therefore, the input emulator 603 is adapted to be connected with theoutput of the infusion pump 102, whereas the skin temperature emulator604, the response emulator 605, and the variable skin resistanceemulator 606 are adapted to be connected with the measuring means 103.

[0104] When an electrical stimulation is applied to the skin resistanceemulator 606, the artificial patient will emulate/generate amovement/reaction (muscle contraction/reaction) of the response emulator605 which can be measured by the same kind of transducer normallyapplied to a real patient being monitored. If the AP receives musclerelaxants by infusion, i.e. if muscle relaxant is received by the inputemulator 603, the AP will response to the stimulation and the responsewill depend on the stimulation given, the set skin/body temperature, theamount of drug infused and the time since infusion. Furthermore, the APwill emulate the surface temperature of the patient, as this is animportant factor, which influences the muscle contraction responses. Inother words, the AP behaves like a real patient.

[0105] Compared to the state of the art pre-clinical/clinical testing, alarger number of tests cases, including abnormal situations andstability, can be simulated and tested by means of the AP, in a way thatis normally not possible. In addition a well-documented verificationrecord can be obtained when using the AP in tests. This is a majorimprovement in validation of system safety and efficacy compared tosystems according to the prior art. The control and registrationmechanisms of the AP may advantageously be used for initial testing ofthe system pilots and 0-series before these are tested on real patientsto demonstrate the safety and efficacy of the systems. Further, the APmay advantageously be used for training and educating users in how asystem for administering muscle relaxant to a patient is optimallyoperated, e.g. prior to using the system on real patients.

[0106] The evaluations performed with the artificial patientspecifically allow verification of the system stability and of hazardanalysis actions, in a way that is not possible during clinical trials.

[0107] The test system according to the invention enables an evaluationand validation of the widest possible range of patient, interactions ina pre-clinical in-vitro setting.

[0108] While a preferred embodiment of the invention has beenillustrated and described herein, it will be apparent to those skilledin the art that modifications and improvements may be made to formsherein specifically disclosed. Accordingly, the present invention is notto be limited to the forms therein specifically disclosed. For example,the system may be included in other instruments used in relation tosurgical procedures.

1. A system for administering muscle relaxant to a patient, said systemincluding: an infusion pump adapted for delivering said muscle relaxantto a patient, a controller adapted for controlling the operation of saidinfusion pump on the basis of at least one received input value, andmeasuring means adapted for continuously measuring the effect of saidmuscle relaxant on the patient, and adapted for supplying a valuerepresenting said measured effect as said input value to saidcontroller, wherein on basis of said at least one input value, saidcontroller is adapted for selecting a control value from a set ofpredetermined control values as the value to be used for controllingsaid infusion pump, characterised in that said measuring means isadapted for stimulating a muscle of the patient by a number ofsucceeding electric or magnetic pulses, for measuring the resultingmuscle reaction pulses and for using the number of muscle reactionpulses as said input value.
 2. A system according to claim 1,characterised by including a memory with an array of one or moredimensions holding said set of predefined control values, where saidcontroller is adapted for selecting a control value from said set ofcontrol values by indexing said array by said at least one input valueand/or at least one value derived therefrom.
 3. A system according toclaim 2, characterised in that said array is adapted for including oneor more mathematical functions as a representation of a number of saidcontrol values.
 4. A system according to one or more of claims 1-3,characterised in that said controller is adapted for selecting thecontrol value or a representation thereof on the basis of at least oneindex value derived from two or more previously received input values.5. A system according to claim 4, characterised in that said at leastone index value includes a value derived as the mean value of two ormore previously received input values.
 6. A system according to one ormore of the preceding claims, characterised in that said measuring meansis adapted for comparing two or more of said measured muscle reactionpulses with two or more corresponding reference muscle reaction pulsesor a representation thereof, and determining the difference therebetween as an effect of direct muscle stimulation.
 7. A system accordingto one or more of the preceding claims, characterised in that saidsystem is adapted for subtracting said effect of direct musclestimulation from the measured effect of said muscle relaxant deliveredto the patient.
 8. A system according to one or more of the precedingclaims, characterised in that said infusion pump is adapted forincepting a container including muscle relaxant and for deliveringmuscle relaxant from said container to a patient and by furtherincluding identification means adapted for identifying the containerincepted in the infusion pump.
 9. A system according to claim 8,characterised in that said controller includes a plurality of sets ofcontrol values, and said controller is adapted for selecting a set ofcontrol values to be used on the basis of the identification of thecontainer incepted in the infusion pump.
 10. A system according to claim8 or 9, characterised in that said controller includes a plurality ofsets of control values, and said controller is adapted for selecting aset of control values to be used on the basis of a received valuerepresenting the type of intervention performed or to be performed or isdependent upon certain specific patient characteristics.
 11. A method ofadministering muscle relaxant to a patient, said method including:delivering said muscle relaxant to a patient, where delivery iscontrolled on the basis of at least one received input value, andcontinuously measuring the effect of said muscle relaxant on thepatient, and supplying a value representing said measured effect as saidinput value for said controlling, characterised in that said controllingis performed using a set of predetermined control values and furtherincluding selecting of a control value from said set of control valuesas the value to be used for controlling said infusion pump, where saidselection is based on said input value and/or a value derived therefrom.12. A method according to claim 11, characterised in that said valueselection is performed on the basis of at least one index value derivedfrom two or more previously received input values.
 13. A methodaccording to claim 12, characterised in that said at least one indexvalue is determined as the mean value of two or more previously receivedinput values.
 14. A testing apparatus adapted to be used for testing theoperation of a system for administering muscle relaxant to a patient,characterised in that, said testing apparatus includes: an inputemulator adapted for receiving muscle relaxant from said system; atesting signal receiver adapted for receiving a testing signal from saidsystem; a test controller adapted for continuously determining a valuerepresenting the present level of relaxation of a patient simulated bythe apparatus, said value being determined on basis of the amount ofrelaxant infused and the time elapsed since infusion; and a responseemulator adapted for generating an output signal in response to saidreceived testing signal, said output signal reflecting the present stateof relaxation.
 15. A testing system according to claim 14, characterisedin that, said input emulator is a weighing instrument or a flowmeasuring device.
 16. A testing system according to claim 14 or 15,characterised in that, said response emulator is an accelerationgenerator, a force generator, a sound generator or an electromyographygenerator.